Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.

Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecular...

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Autores principales: Naoya Maekawa, Satoru Konnai, Ryoyo Ikebuchi, Tomohiro Okagawa, Mami Adachi, Satoshi Takagi, Yumiko Kagawa, Chie Nakajima, Yasuhiko Suzuki, Shiro Murata, Kazuhiko Ohashi
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Publicado: Public Library of Science (PLoS) 2014
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spelling oai:doaj.org-article:274bebba5da1467db46e1e7a242b93a02021-11-18T08:16:15ZExpression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.1932-620310.1371/journal.pone.0098415https://doaj.org/article/274bebba5da1467db46e1e7a242b93a02014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24915569/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.Naoya MaekawaSatoru KonnaiRyoyo IkebuchiTomohiro OkagawaMami AdachiSatoshi TakagiYumiko KagawaChie NakajimaYasuhiko SuzukiShiro MurataKazuhiko OhashiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 6, p e98415 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Naoya Maekawa
Satoru Konnai
Ryoyo Ikebuchi
Tomohiro Okagawa
Mami Adachi
Satoshi Takagi
Yumiko Kagawa
Chie Nakajima
Yasuhiko Suzuki
Shiro Murata
Kazuhiko Ohashi
Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
description Programmed death 1 (PD-1), an immunoinhibitory receptor, and programmed death ligand 1 (PD-L1), its ligand, together induce the "exhausted" status in antigen-specific lymphocytes and are thus involved in the immune evasion of tumor cells. In this study, canine PD-1 and PD-L1 were molecularly characterized, and their potential as therapeutic targets for canine tumors was discussed. The canine PD-1 and PD-L1 genes were conserved among canine breeds. Based on the sequence information obtained, the recombinant canine PD-1 and PD-L1 proteins were constructed; they were confirmed to bind each other. Antibovine PD-L1 monoclonal antibody effectively blocked the binding of recombinant PD-1 with PD-L1-expressing cells in a dose-dependent manner. Canine melanoma, mastocytoma, renal cell carcinoma, and other types of tumors examined expressed PD-L1, whereas some did not. Interestingly, anti-PD-L1 antibody treatment enhanced IFN-γ production from tumor-infiltrating cells. These results showed that the canine PD-1/PD-L1 pathway is also associated with T-cell exhaustion in canine tumors and that its blockade with antibody could be a new therapeutic strategy for canine tumors. Further investigations are needed to confirm the ability of anti-PD-L1 antibody to reactivate canine antitumor immunity in vivo, and its therapeutic potential has to be further discussed.
format article
author Naoya Maekawa
Satoru Konnai
Ryoyo Ikebuchi
Tomohiro Okagawa
Mami Adachi
Satoshi Takagi
Yumiko Kagawa
Chie Nakajima
Yasuhiko Suzuki
Shiro Murata
Kazuhiko Ohashi
author_facet Naoya Maekawa
Satoru Konnai
Ryoyo Ikebuchi
Tomohiro Okagawa
Mami Adachi
Satoshi Takagi
Yumiko Kagawa
Chie Nakajima
Yasuhiko Suzuki
Shiro Murata
Kazuhiko Ohashi
author_sort Naoya Maekawa
title Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
title_short Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
title_full Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
title_fullStr Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
title_full_unstemmed Expression of PD-L1 on canine tumor cells and enhancement of IFN-γ production from tumor-infiltrating cells by PD-L1 blockade.
title_sort expression of pd-l1 on canine tumor cells and enhancement of ifn-γ production from tumor-infiltrating cells by pd-l1 blockade.
publisher Public Library of Science (PLoS)
publishDate 2014
url https://doaj.org/article/274bebba5da1467db46e1e7a242b93a0
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